Biomarkers in Rheumatoid Arthritis Treated With Anti-interleukin-6 Therapy

NCT04281602 | Unknown

• 1 other identifier: 2019-A01557-50
• Study Type: observational
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The use of anti-interleukin (IL)-6 therapy, including tocilizumab, in rheumatoid arthritis or giant cell arteritis, led to the improvement or even control of disease in some patients for whom no further therapeutic options were available. Nevertheless, the evaluation of the efficacy of these treatments are negatively impacted by the lack of reliable biomarkers. Indeed, usual inflammatory biomarkers used during the follow-up of these patients to detect persistent disease activity or intercurrent infection, such as C-reactive protein, fibrinogen and procalcitonin, are dependant on IL-6. Thse usual biomarkers cannot therefore be reliably used during anti-IL-6 therapy. Some other experimental biomarkers are totally or partially independent of IL-6, or even of inflammasome, and thus are credible candidates for the follow-up of patients treated with anti-IL-6 therapy. Here investigators propose a controlled, prospective, monocentric, observational study evaluating several biomarkers, usual and experimental, in patients suffering from rheumatoid arthritis treated with anti-IL-6 therapy. This study will include 25 patients suffering from rheumatoid arthritis requiring an anti-IL-6 therapy and 25 healthy controls. In patients suffering from rheumatoid arthritis, usual and experimental biomarkers will be assessed at D0, D15, W24 and W52 from the introduction of anti-IL-6 therapy, or during an intercurrent infection. Investigators thus hypothesized that experimental biomarker levels will still be increased at D15, contrary to usual biomarkers dependant on IL-6 which will be normal whereas rheumatoid arthritis is still active based on usual radiological and clinical criteria, and that all biomarkers will be normal a W24.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (2)

• Levels of usual biomarkers (C-reactive protein, fibrinogen, procalcitonin, serum protein electrophoresis)

  C-reactive protein and fibrinogen measured by turbidimetry; procalcitonin by an enzyme immunoassay kit, serum protein electrophoresis by electrophoresis

  Day 15

• Levels of experimental biomarkers (IL-8, IL-1beta, IL-1RA, IL-4, IL-5, IL-6, IL-10, IL-12/23, IL-17, IL-18, IL-21, IFN-gamma, TNF-alpha, TGF-beta, S100 proteins, ceruloplasmin, C3, C4, CH50, serum amyloid A, factor VIII, neutrophil/lymphocyte ratio)

  IL-8, IL-1beta, IL-1RA, IL-4, IL-5, IL-6, IL-10, IL-12/23, IL-17, IL-18, IL-21, IFN-gamma, TNF-alpha, TGF-beta and S100 proteins measured by Meso Scale Discovery assay, ceruloplasmin, C3, C4, serum amyloid A by nephelometry, CH50 by an enzyme immunoassay kit, factor VIII by turbidimetry, neutrophil/lymphocyte ratio by an automated method

  Day 15

Secondary Outcomes (6)

• Levels of usual biomarkers (C-reactive protein, fibrinogen, procalcitonin, serum protein electrophoresis)

  Day 15 compared to Day 0

• Levels of experimental biomarkers (IL-8, IL-1beta, IL-1RA, IL-4, IL-5, IL-6, IL-10, IL-12/23, IL-17, IL-18, IL-21, IFN-gamma, TNF-alpha, TGF-beta, S100 proteins, ceruloplasmin, C3, C4, CH50, serum amyloid A, factor VIII, neutrophil/lymphocyte ratio)

  Day 15 compared to Day 0

• Levels of usual biomarkers (C-reactive protein, fibrinogen, procalcitonin, serum protein electrophoresis, erythrocyte sedimentation rate)

  Week 24 compared to Day 15

• Levels of experimental biomarkers (IL-8, IL-1beta, IL-1RA, IL-4, IL-5, IL-6, IL-10, IL-12/23, IL-17, IL-18, IL-21, IFN-gamma, TNF-alpha, TGF-beta, S100 proteins, ceruloplasmin, C3, C4, CH50, serum amyloid A, factor VIII, neutrophil/lymphocyte ratio)

  Week 24 compared to Day 15

• Levels of usual biomarkers (C-reactive protein, fibrinogen, procalcitonin, serum protein electrophoresis, erythrocyte sedimentation rate)

  Within 72 hours following infection occuring after week 24

Study Arms (2)

Rheumatoid arthritis patients

Adult patients suffering from rheumatoid arthritis, diagnosed according to American College of Rheumatology/European League Against Rheumatism 2010 criteria and requiring a anti-IL-6 treatment

Healthy controls

Healthy controls not suffering from acute or chronic inflammatory disease at inclusion.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients and healthy controls followed at Caen, university hospital, in the department of rhumatology or internal medicine

You may qualify if:

• Adult patients suffering from rheumatoid arthritis diagnosed according to American College of Rheumatology/European League Against Rheumatism 2010 criteria and requiring an anti-IL-6 therapy by intravenous or subcutaneous injection
• Non-opposition of the patient
• Non-opposition of the subject

You may not qualify if:

• Patient is already treated with anti-IL-6 therapy
• Pregnancy or breastfeeding women
• Person under judicial protection, guardianship
• Patient suffering from another chronic inflammatory disease
• Person not beneficiaries of the social security system
• Pregnancy or breastfeeding women
• Person under judicial protection, guardianship
• Previous history of chronic inflammatory disease
• Ongoing anti-inflammatory or immunosuppressive treatment, except aspirin and derivatives at anti-platelet aggregation dose, non-steroidal anti-inflammatory drugs stopped for 10 days or systemic steroids stopped for 1 month
• Person not beneficiaries of the social security system

Sponsors & Collaborators

• University Hospital, Caen: lead

Study Sites (1)

CHU de Caen Normandie

Caen, 14000, France

RECRUITING

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Samuel Deshayes, MD

CONTACT

+33231064579; deshayes-s@chu-caen.fr

Achille Aouba, MD PhD

CONTACT

+33231064579; aouba-a@chu-caen.fr

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2019
• First Posted: February 24, 2020
• Study Start: February 18, 2020
• Primary Completion: January 2, 2023
• Study Completion: May 2, 2024
• Last Updated: March 4, 2020

Record last verified: 2020-03

Locations

FR (1)